Dataset Information

Olfactory Receptor-Related Duplicons Mediate a Microdeletion at 11q13.2q13.4 Associated with a Syndromic Phenotype.

ABSTRACT: By array-CGH, we identified a cryptic deletion of about 3.4 Mb involving the chromosomal region 11q13.2q13.4 in a child with speech and developmental delay. Highly homologous segmental duplications related to the well-known olfactory receptor (OR)-containing clusters at 8p and 4p are located at the breakpoints of the imbalance and may be involved in its occurrence. Although these structural features are known to promote recurrent chromosomal rearrangements and previous studies had included the 11q13.2q13.4 deletion region among those considered potentially more unstable, neither deletions nor duplications of this region had been reported until now. Among the deleted genes, SHANK2 might play a role in the phenotype of the patient since it encodes a postsynaptic scaffolding protein similar to SHANK3, whose haploinsufficiency is a well-known cause of severe speech delay and autistic-like behavior, and recently deletions and mutations of SHANK2 have been described in patients with an autistic spectrum disorder or mental retardation.

SUBMITTER: Wischmeijer A

PROVIDER: S-EPMC3042121 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Publications

Olfactory Receptor-Related Duplicons Mediate a Microdeletion at 11q13.2q13.4 Associated with a Syndromic Phenotype.

Wischmeijer A A Magini P P Giorda R R Gnoli M M Ciccone R R Cecconi L L Franzoni E E Mazzanti L L Romeo G G Zuffardi O O Seri M M

Molecular syndromology 20101125 4

By array-CGH, we identified a cryptic deletion of about 3.4 Mb involving the chromosomal region 11q13.2q13.4 in a child with speech and developmental delay. Highly homologous segmental duplications related to the well-known olfactory receptor (OR)-containing clusters at 8p and 4p are located at the breakpoints of the imbalance and may be involved in its occurrence. Although these structural features are known to promote recurrent chromosomal rearrangements and previous studies had included the 1 ...[more]

PMID: 21373257

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Project description:BackgroundIn vertebrates and invertebrates, sensory neurons adapt to variable ambient conditions, such as the duration or repetition of a stimulus, a physiological mechanism considered as a simple form of non-associative learning and neuronal plasticity. Although various signaling pathways, as cAMP, cGMP, and the inositol 1,4,5-triphosphate receptor (InsP3R) play a role in adaptation, their precise mechanisms of action at the cellular level remain incompletely understood. Recently, in Drosophila, we reported that odor-induced Ca2+-response in axon terminals of olfactory receptor neurons (ORNs) is related to odor duration. In particular, a relatively long odor stimulus (such as 5 s) triggers the induction of a second component involving intracellular Ca2+-stores.ResultsWe used a recently developed in-vivo bioluminescence imaging approach to quantify the odor-induced Ca2+-activity in the axon terminals of ORNs. Using either a genetic approach to target specific RNAs, or a pharmacological approach, we show that the second component, relying on the intracellular Ca2+-stores, is responsible for the adaptation to repetitive stimuli. In the antennal lobes (a region analogous to the vertebrate olfactory bulb) ORNs make synaptic contacts with second-order neurons, the projection neurons (PNs). These synapses are modulated by GABA, through either GABAergic local interneurons (LNs) and/or some GABAergic PNs. Application of GABAergic receptor antagonists, both GABAA or GABAB, abolishes the adaptation, while RNAi targeting the GABABR (a metabotropic receptor) within the ORNs, blocks the Ca2+-store dependent component, and consequently disrupts the adaptation. These results indicate that GABA exerts a feedback control. Finally, at the behavioral level, using an olfactory test, genetically impairing the GABABR or its signaling pathway specifically in the ORNs disrupts olfactory adapted behavior.ConclusionTaken together, our results indicate that a relatively long lasting form of adaptation occurs within the axon terminals of the ORNs in the antennal lobes, which depends on intracellular Ca2+-stores, attributable to a positive feedback through the GABAergic synapses.

Dataset Information

Olfactory Receptor-Related Duplicons Mediate a Microdeletion at 11q13.2q13.4 Associated with a Syndromic Phenotype.

Publications

Olfactory Receptor-Related Duplicons Mediate a Microdeletion at 11q13.2q13.4 Associated with a Syndromic Phenotype.

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